This invention relates to a multistep chiral process for selectively obtaining high yields of 1-.beta.-methylcarbapenem intermediates for the subsequent synthesis of 1-.beta.-methylcarbapenem antibiotics. The process involves introducing an exocyclic .alpha.-methylene double bond into a bicyclic .beta.-lactam ring structure by means of .alpha.-alkylation, followed by .alpha.-selenation and then oxidation to form the exocyclic .alpha.-olefin, and then reduction to form the amine-alcohol, followed by cyclization to form a bridging-protecting group. The exocyclic double bond is then subjecting the compound to hydrogenation conditions with a metallic nickel hydrogenation catalyst which preferentially results in the formation of the 1-.beta.-methylcarbapenem intermediate.
1-.beta.-Methylcarbapenems, as described in the reference Heterocycles, 1984, Vol. 21, pp. 29-40 by D. H. Shih, F. Baker, L. Cama and B. G. Christensen, are extremely useful and effective broad spectrum antibiotics, useful against a wide variety of bacteria including Gram-positive bacteria including S. aureus, Strep. sp., B. subtilis, and Gram-negative bacteria such as E. coli, Shigella sp., Enterobacter sp., Klebsiella sp., Proteus, Serratia and Pseudomonas sp.
A method of synthesizing 1-.beta.-methylcarbapenems is described in the above-cited reference in which the beta-methyl chirality is introduced into the molecule by base-catalyzed alkylation producing a mixture of .alpha. and .beta. isomers which are separated by chromatographic procedures.
However, because of the relatively low .beta./ .alpha. epimeric ratio obtained by this alkylation route, newer methods for obtaining the desired .beta.-methyl intermediate on a larger scale are constantly being sought.